In a 66‑year‑old woman on methotrexate presenting with rectal bleeding, a shortened activated partial thromboplastin time (APTT) of 23.8 seconds, mild anemia (hematocrit 33.2 %), and mild leukocytosis (white‑cell count 11.4 ×10⁹/L), what is the appropriate management?

Management of Rectal Bleeding in a 66-Year-Old Woman on Methotrexate

This patient requires immediate colonoscopy to identify the bleeding source, packed red blood cell transfusion to correct anemia (target hemoglobin ≥10 g/dL), and urgent hematology consultation to evaluate methotrexate-induced bone marrow suppression. 1, 2, 3

Immediate Priorities

Resuscitation and Hemodynamic Stabilization

• Establish large-bore intravenous access (two large-bore cannulae in antecubital fossae) immediately to enable rapid transfusion and fluid administration 1
• Begin packed red blood cell transfusion without delay to restore oxygen-carrying capacity, targeting hemoglobin ≥10 g/dL in the setting of active bleeding and symptomatic anemia (current Hgb 11.4 g/dL with ongoing blood loss) 1
• Maintain mean arterial pressure >65 mmHg during resuscitation while monitoring for adequate tissue perfusion (mental status, urine output >30 mL/h, capillary refill) 4, 1
• Limit crystalloid administration to 1-2 liters maximum to avoid dilutional effects and fluid overload 1

Urgent Diagnostic Evaluation

• Arrange urgent colonoscopy within 24 hours to identify and potentially treat the bleeding source, as hemorrhoids alone do not cause significant anemia and proximal colonic pathology (including malignancy) must be excluded 4, 2
• The risk of colorectal cancer in patients presenting with rectal bleeding ranges from 2.4% to 11%, making full colonic evaluation essential 2
• Never attribute anemia (Hct 33.2%) to hemorrhoids without complete colonic evaluation—this is a critical error that could delay cancer diagnosis 2

Methotrexate-Related Concerns

Hematologic Toxicity Assessment

• Hold methotrexate immediately and obtain urgent hematology consultation to evaluate for drug-induced bone marrow suppression 3
• The FDA label emphasizes that methotrexate has potential for serious toxicity at any dose, and toxic effects can occur at any time during therapy 3
• Obtain complete blood count with differential and platelet count, peripheral blood smear, reticulocyte count, vitamin B12, and folate levels to assess for megaloblastic anemia or pancytopenia 3, 5
• Methotrexate can cause isolated erythrocytic bone marrow suppression with severe megaloblastic anemia, and an elevated mean corpuscular volume may indicate folate deficiency and impending toxicity 5
• The WBC of 11.4 × 10⁹/L suggests leukocytosis rather than leukopenia, which may indicate infection or inflammatory response rather than bone marrow suppression 3

Risk Factors for Methotrexate Toxicity

• Assess renal function immediately (creatinine, BUN, estimated GFR), as decreased renal function is a major risk factor for methotrexate toxicity 3
• Review all concurrent medications, particularly NSAIDs, which should not be administered concomitantly with methotrexate due to risk of elevated and prolonged serum methotrexate levels causing severe hematologic and gastrointestinal toxicity 3
• Older age (this patient is 66 years old) is an independent risk factor for methotrexate toxicity due to diminished hepatic and renal function and decreased folate stores 3

Coagulation Assessment

Shortened APTT Interpretation

• The shortened APTT of 23.8 seconds is not a contraindication to necessary procedures and does not explain the bleeding 4, 6
• A shortened APTT may indicate a hypercoagulable state or elevated factor VIII levels, but does not cause bleeding 6, 7
• A prolonged APTT would be concerning for bleeding risk, but this patient has a shortened value, which is the opposite finding 4, 6
• The APTT tests the intrinsic clotting pathway and is used primarily to monitor heparin therapy; a shortened value has no bearing on bleeding risk from gastrointestinal pathology 6, 7

Additional Coagulation Studies

• Obtain prothrombin time/INR, fibrinogen level, and platelet count to complete the coagulation assessment before any invasive procedures 4, 8
• Methotrexate can cause isolated thrombocytopenia even after a single dose, so platelet count monitoring is essential 9

Endoscopic Intervention

Colonoscopy Indications and Timing

• Perform urgent colonoscopy (within 24 hours) with gastroenterology consultation for both diagnosis and potential therapeutic intervention 4, 1
• Anemia from hemorrhoids is extremely rare (0.5 per 100,000 population per year), and complete colonic evaluation is specifically indicated when bleeding is associated with anemia 2
• If colonoscopy reveals no proximal source and hemorrhoids are confirmed, endoscopic hemorrhoid ligation or sclerotherapy can be performed to control bleeding 4

Bleeding Control Strategies

• Local endoscopic procedures (endoscopic band ligation, sclerotherapy) should be used to arrest bleeding where feasible 4
• If endoscopy fails to identify or control the source, consider CT angiography or interventional radiology consultation for embolization 4

Ongoing Management

Monitoring and Supportive Care

• Monitor hemoglobin levels closely (every 6-12 hours initially) until bleeding is controlled and hemoglobin stabilizes 4
• Insert urinary catheter to monitor hourly urine output (target >30 mL/h) as a marker of adequate perfusion 1
• Actively warm the patient and all transfused blood products to prevent hypothermia-induced coagulopathy 1
• Correct any acidosis with appropriate resuscitation, as acidosis worsens coagulopathy 1, 8

Methotrexate Management Decisions

• Do not restart methotrexate until hematology has completed evaluation and the bleeding source is identified and treated 3
• If methotrexate-induced toxicity is confirmed, consider leucovorin calcium rescue 3
• Initiate folic acid supplementation (1 mg daily) if methotrexate is to be continued in the future, as this may prevent hematologic toxicity 4, 5

Critical Pitfalls to Avoid

• Never assume hemorrhoids are the cause of anemia without full colonoscopy—operating on hemorrhoids without excluding proximal pathology is a critical error 2
• Never delay colonoscopy in a patient with rectal bleeding and anemia, as the risk of colorectal malignancy is substantial (2.4-11%) 2
• Never continue methotrexate in the setting of unexplained anemia and active bleeding without hematology evaluation 3
• Never attribute positive fecal occult blood to hemorrhoids until the colon is adequately evaluated 2
• Never use excessive crystalloid resuscitation (>1-2 liters) in anemic patients, as this worsens dilutional effects without addressing oxygen delivery 1